GLA p.Arg342Ter
c.1024C>T · rs104894843 · VCV10743
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 13 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
GLA-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.53 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GLA
- Protein
- p.Arg342Ter
- Coding
- c.1024C>T
- MANE Select
- NM_000169
- dbSNP
- rs104894843
- Type
- single nucleotide variant
- Location
- chrX:101398075 (GRCh38)
- Structure
- AlphaFold pLDDT 94.45 · 31 PDB
- Residue 342
- a UniProt-annotated variant site (in fabryd; loss of enzyme activity); a UniProt-annotated variant site (in fabryd); a β-strand
Similar variants
- GLA p.Arg342Gln Pathogenic ★★ same residue
- GLA p.Arg342Leu Pathogenic ★ same residue
- GLA p.Arg342Pro Likely pathogenic ★ same residue
- GLA p.Arg342fs Pathogenic ★ same residue
- GLA p.Arg342Gly Likely pathogenic ★ same residue
- GLA c.1000-10G>A Likely pathogenic ★★ same condition
- GLA c.1000-1G>A Pathogenic ★★ same condition
- GLA c.1000-1G>C Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gla-p-arg342ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown